A novel reciprocal and biphasic relationship between membrane cholesterol and beta-secretase activity in SH-SY5Y cells and in human platelets.

Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the A beta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.

Credit Unions: A Theoretical and Empirical Overview

In 2009 there were over 49,330 credit unions across 98 countries with more than 184 million members and approximately $1,354 billion in assets. There is a great diversity within the credit union movement across these countries. This reflects the various economic, historic and cultural contexts within which credit unions operate. This paper traces the evolution of the credit union movement. It examines credit union objectives, and considers issues relating to efficiency, technology adoption, product diversification, merger, failure and demutualization. The regulatory environment within which credit unions operate is also explored under the themes of interest rate regulation, common bond requirements, taxation, deposit insurance and capital regulation. The overview also considers demutualization and the costs and benefits to credit unions of altering their organizational form.

Measurement of DNA damage by electrons with energies between 25 and 4000 eV.

All ionizing radiations deposit energy stochastically along their tracks. The resulting distribution of energies deposited in a small target such as the DNA helix leads to a corresponding spectrum in the severity of damage produced. So far, most information about the probable spectra of DNA lesion complexity has come from Monte Carlo studies which endeavour to model the relationship between the energy deposited in DNA and the damage induced. The aim of this paper is to establish methods of determining this relationship by irradiating pBR322 plasmid DNA using low energy electrons with energies comparable with the minimum energy thought to produce critical damage. The technique of agarose gel electrophoresis has been used to ascertain the fraction of DNA single- and double-strand breaks induced by monoenergetic electrons with energies as low as 25 eV. Our data show that the threshold electron energy for induction of single-strand breaks is

Information disclosure and depositor discipline in the Chinese banking sector

We investigate the relationship between information disclosure and depositor behaviour in the Chinese banking sector. Specifically, we enquire whether enhanced information disclosure enables investors to more effectively infer a banking institution's risk profile, thereby influencing their deposit decisions. Utilising an unbalanced panel, incorporating financial data from 169 Chinese banks over the 1998–2009 period, we employ generalised-method-of-moments (GMM) estimation procedures to control for potential endogeneity, unobserved heterogeneity, and persistence in the dependent variable. We uncover evidence that: (i) the growth rate of deposits is sensitive to bank fundamentals after controlling for macroeconomic factors, diversity in ownership structure, and government intervention; (ii) a bank publicly disclosing more transparent information in its financial reports, is more likely to experience growth in its deposit base; and (iii) banks characterised by high information transparency, well-capitalised and adopted international accounting standards, are more able to attract funds by offering higher interest rates.

Missing Links, Cultural Modernity and the Dead: Anatomically Modern Humans in the Great Cave of Niah (Sarawak, Borneo)

The Great Cave of Niah in Sarawak (northern Borneo) came into the gaze of Western Science through the work of Alfred Russell Wallace, who came to Sarawak in the 1850s to search for ‘missing links’ in his pioneering studies of evolution and the natural history of Island Southeast Asia and Australasia. The work of Tom and Barbara Harrisson in the 1950s and 1960s placed the Great Cave, and particularly their key find, the ‘Deep Skull’, at the nexus of the evolving archaeological framework for the region: for decades the skull, dated in 1958 by adjacent charcoal to c.40,000 BP, was the oldest fossil of an anatomically modern human anywhere in the world and thus critical to ideas about human evolution and dispersal. Although several authorities later questioned the provenance and antiquity of the Deep Skull, renewed investigations of the Harrisson excavations since 2000 have shown that it can be attributed securely to a specific location in the Pleistocene stratigraphy, with direct U-series dating on a piece of the skull indicating an age for it of c.37,500 BP and the first evidence for associated human activity at the site going back to c.50,000 BP. The new work also indicates that the skull is part of a cultural deposit, perhaps a precursor to the long tradition in Borneo of processing of the dead and secondary burial. These indicators of cultural complexity chime with the complexity of the subsistence behaviour of the early users of the caves discussed by Philip Piper and Ryan Rabett in chapter ten of this volume.

Deriving the Railway Mania

This article argues that the promotion boom which occurred in the railway industry during the mid 1840s was amplified by the issue of derivative-like assets, which let investors take highly leveraged positions in the shares of new railway companies. The partially paid shares which the new railway companies issued allowed investors to obtain exposure to an asset by paying only a small initial deposit. The consequence of this arrangement was that investor returns were substantially amplified, and many schemes could be financed simultaneously. However, when investors were required to make further payments it put a negative downward pressure on prices.

Identification of last interglacial deposits in eastern Beringia: a cautionary note from the Palisades, interior Alaska

Last interglacial sediments in unglaciated Alaska and Yukon (eastern Beringia) are commonly identified by palaeoecological indicators and stratigraphic position ~2-5m above the regionally prominent Old Crow tephra (124±10ka). We demonstrate that this approach can yield erroneous age assignments using data from a new exposure at the Palisades, a site in interior Alaska with numerous exposures of last interglacial sediments. Tephrochronology, stratigraphy, plant macrofossils, pollen and fossil insects from a prominent wood-rich organic silt unit are all consistent with a last interglacial age assignment. However, six 14C dates on plant and insect macrofossils from the organic silt range from non-finite to 4.0 14C ka BP, indicating that the organic silt instead represents a Holocene deposit with a mixed-age assemblage of organic material. In contrast, wood samples from presumed last interglacial organic-rich sediments elsewhere at the Palisades, in a similar stratigraphic position with respect to Old Crow tephra, yield non-finite 14C ages. Given that local permafrost thaw since the last interglaciation may facilitate reworking of older sediments into new stratigraphic positions, minimum constraining ages based on 14C dating or other methods should supplement age assignments for last interglacial sediments in eastern Beringia that are based on palaeoecology and stratigraphic association with Old Crow tephra.

A Silurian armoured aplacophoran and implications for molluscan phylogeny

The Mollusca is one of the most diverse, important and well-studied invertebrate phyla; however, relationships among major molluscan taxa have long been a subject of controversy(1-9). In particular, the position of the shell-less vermiform Aplacophora and its relationship to the better-known Polyplacophora (chitons) have been problematic: Aplacophora has been treated as a paraphyletic or monophyletic group at the base of the Mollusca(3,6,8), proximate to other derived clades such as Cephalopoda(2,3,10), or as sister group to the Polyplacophora, forming the clade Aculifera(1,5,7,11,12). Resolution of this debate is required to allow the evolutionary origins of Mollusca to be reconstructed with confidence. Recent fossil finds(13-16) support the Aculifera hypothesis, demonstrating that the Palaeozoic-era palaeoloricate 'chitons' included taxa combining certain polyplacophoran and aplacophoran characteristics(5). However, fossils combining an unambiguously aplacophoran-like body with chiton-like valves have remained elusive. Here we describe such a fossil, Kulindroplax perissokomos gen. et sp. nov., from the Herefordshire Lagerstatte(17,18) (about 425 million years BP), a Silurian deposit preserving a marine biota(18) in unusual three-dimensional detail. The specimen is reconstructed three-dimensionally through physical-optical tomography(19). Phylogenetic analysis indicates that this and many other palaeoloricate chitons are crown-group aplacophorans.

Evaluation of corneal endothelium and keratic precipitates by specular microscopy in anterior uveitis

Background - The study of corneal endothelium, by specular microscopy, in patients with anterior uveitis has largely been restricted to observations on the endothelial cells. In this prospective study 'keratic precipitates' (KP) in different types of uveitis were examined in different stages of the disease process and the endothelial changes occurring in the vicinity of the KP were evaluated in comparison with the endothelium of the uninvolved eye. Methods - 13 patients with active unilateral uveitis were recruited. The mean age was 42.9 years (range 20-76 years). A Tomey-1100 contact wide field specular (x10) microscope was used to capture endothelial images and KP until the resolution of uveitis. Data regarding type of uveitis, number, size, and nature of KP were recorded. Automated morphometric analysis was done for cell size, cell density and coefficient of variation, and statistical comparisons of cell size and cell density were made (Student's t test) between the endothelium in the vicinity of fresh and resolving KP, fresh KP and normal endothelium, and resolving KP and normal endothelium. Results - On specular microscopy, fresh KP were seen as dense, white glistening deposits occupying 5-10 endothelial cells in diameter and fine KP were widely distributed and were one or two endothelial cells in diameter. The KP in Posner-Schlossman syndrome had a distinct and different morphology. With clinical remission of uveitis, the KP were observed to undergo characteristic morphological changes and old KP demonstrated a large, dark halo surrounding a central white deposit and occasionally a dark shadow or a 'lacuna' replaced the site of the original KP. Endothelial blebs were noted as dark shadows or defects in the endothelial mosaic in patients with recurrent uveitis. There was significant statistical difference in the mean cell size and cell density of endothelial cells in the vicinity of fresh KP compared with normal endothelium of the opposite eye. Conclusion - This study elucidated the different specular microscopic features of KP in anterior uveitis. Distinct morphological features of large and fine KP were noted. These features underwent dramatic changes on resolution of uveitis. The endothelium was abnormal in the vicinity of KP, which returned to near normal values on resolution of uveitis.

A spectroscopic study of the chemistry and reactivity of SO2 on Pt{111}: Reactions with O-2, CO and C3H6

The chemisorption and reactivity of SO2 on Pt{111} have been studied by HREELS, XPS, NEXAFS and temperature-programmed desorption. At 160 K SO2 adsorbs intact at high coverages, with eta(2) S-O coordination to the surface. On annealing to 270 K, NEXAFS indicates the SO2 molecular plane essentially perpendicular to the surface. Preadsorbed O-a reacts with SO2 to yield adsorbed SO4, identified as the key surface species responsible for SO2-promoted catalytic alkane oxidation. Coadsorbed CO or propene efficiently reduce SO2 overlayers to deposit S-a, and the implications of this for catalytic systems are discussed.

Structural reinforcement of microvascular networks using electrostatic layer-by-layer assembly with halloysite nanotubes

We demonstrate a method for tailoring local mechanical properties near channel surfaces of vascular structural polymers in order to achieve high structural performance in microvascular systems. While synthetic vascularized materials have been created by a variety of manufacturing techniques, unreinforced microchannels act as stress concentrators and lead to the initiation of premature failure. Taking inspiration from biological tissues such as dentin and bone, these mechanical deficiencies can be mitigated by complex hierarchical structural features near to channel surfaces. By employing electrostatic layer-by-layer assembly (ELbL) to deposit films containing halloysite nanotubes onto scaffold surfaces followed by matrix infiltration and scaffold removal, we are able to controllably deposit nanoscale reinforcement onto 200 micron diameter channel surface interiors in microvascular networks. High resolution strain measurements on reinforced networks under load verify that the halloysite reduces strain concentrations and improves mechanical performance.

In Situ Formation of Micron-Scale Li-Metal Anodes with High Cyclability

Scanning probe microscopy methods have been used to electrodeposit and cycle micron-scale Li anodes deposited electrochemically under nanofabricated Au current collectors. An average Li volume of 5 x 10(8) nm(3) was deposited and cycled with 100% coulombic efficiency for similar to 160 cycles. Integrated charge/discharge values agree with before/after topography, as well as in situ dilatometry, suggesting this is a reliable method to study solid-state electrochemical processes. In this work we illustrate the possibility to deposit highly cyclable nanometer thick Li electrodes by mature SPM and nanofab techniques which can pave the way for inexpensive nanoscale battery arrays. 

Long-term mass balance of perennial firn and ice in an Alpine cave (Austria):Constraints from radiocarbon-dated wood fragments

Hundsalm ice cave located at 1520 m altitude in a karst region of western Austria contains up to 7-m-thick deposits of snow, firn and congelation ice. Wood fragments exposed in the lower parts of an ice and firn wall were radiocarbon accelerator mass spectrometry (AMS) dated. Although the local stratigraphy is complex, the 19 individual dates - the largest currently available radiocarbon dataset for an Alpine ice cave - allow to place constraints on the accumulation and ablation history of the cave ice. Most of the cave was either ice free or contained only a small firn and ice body during the 'Roman Warm Period'; dates of three wood fragments mark the onset of firn and ice build-up in the 6th and 7th century ad. In the central part of the cave, the oldest samples date back to the 13th century and record ice growth coeval with the onset of the 'Little Ice Age'. The majority of the ice and firn deposit, albeit compromised by a disturbed stratigraphy, appears to have been formed during the subsequent centuries, supported by wood samples from the 15th to the 17th century. The oldest wood remains found so far inside the ice is from the end of the Bronze Age and implies that local relics of prehistoric ice may be preserved in this cave. The wood record from Hundsalm ice cave shows parallels to the Alpine glacier history of the last three millennia, for example, the lack of preserved wood remains during periods of known glacier minima, and underscores the potential of firn and ice in karst cavities as a long-term palaeoclimate archive, which has been degrading at an alarming rate in recent years. © The Author(s) 2013.

Calculated and observed long term performance of Leneghans embankment

This paper presents the finite element (FE) analysis of the consolidation of the foundation of an embankment constructed over soft clay deposit which shows significant time dependent behaviour and was improved with prefabricated vertical drains. To assess the capability of a simple elastic viscoplastic (EVP) model to predict the long term performance of a geotechnical structure constructed on soft soils, a well documented (Leneghans) embankment was analyzed to predict its long term behaviour characteristics. Two fully coupled two dimensional (2D) plane strain FE analyses have been carried out. In one of these, the foundation of the embankment was modelled with a relatively simpler time dependent EVP model and in the other one, for comparison purposes, the foundation soil was modelled with elasto-plastic Modified Cam-clay (MCC) model. Details of the analyses and the results are discussed in comparison with the field performance. Predictions from the creep (EVP) model were found to be better than those from Elasto-plastic (MCC) analysis. However, the creep analysis requires an additional parameter and additional computational time and resources. © 2011 Taylor & Francis.

Physical and electrochemical evaluation of ATO supported IrO2 catalyst for proton exchange membrane water electrolyser

Antimony doped tin oxide (ATO) was studied as a support material for IrO₂ in proton exchange membrane water electrolyser (PEMWE). Adams fusion method was used to prepare the IrO₂-ATO catalysts. The physical and electrochemical characterisation of the catalysts were carried out using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder conductivity, cyclic voltammetry (CV) and membrane electrode assembly (MEA) polarisation. The BET surface area and electronic conductivity of the supported catalysts were found to be predominantly arisen from the IrO₂. Supported catalyst showed higher active surface area than the pristine IrO₂ in CV analysis with 85% H₃PO₄ as electrolyte. The MEA performance using Nafion®−115 membrane at 80 °C and atmospheric pressure showed a better performance for IrO₂ loading ≥60 wt.% than the pristine IrO₂ with a normalised current density of 1625 mA cm⁻² @1.8 V for the 60% IrO₂-ATO compared to 1341 mA cm⁻² for the pristine IrO₂ under the same condition. The higher performance of the supported catalysts was mainly attributed to better dispersion of active IrO₂ on electrochemically inactive ATO support material, forming smaller IrO₂ crystallites. A 40 wt.% reduction in the IrO₂ was achieved by utilising the support material.